Characterization of the Vitamin D System in Normal and Hypertrophied Heart

描述(由申请人提供)：维生素D直接抑制心肌肥大的关键表型特征，增加了它可能以自分泌或旁分泌的方式发挥作用以抑制肥厚的可能性。然而，要使这一假说成立，需要心肌细胞具有调节和响应维生素D活性形式的能力。维生素D系统的组成部分，特别是VDR、1α-羟基酶和24-羟基酶，将被检测并表征对肥大刺激的反应。维生素D在心血管功能中的重要性得到了维生素D受体(VDR)基因敲除小鼠的研究支持，该小鼠会发展为心肌肥大。然而，考虑到维生素D的多效性，相关的潜在机制很难解释。要确定内源性维生素D对心肌细胞的直接影响需要一个组织特有的模型，因此将产生对心脏选择性缺失的小鼠VDR基因，并将在体内评估对肥大刺激的反应。

DESCRIPTION (provided by applicant): Vitamin D directly inhibits key phenotypic features of cardiac hypertrophy raising the possibility that it may function in an autocrine or paracrine fashion to suppress hypertrophy. However, for this hypothesis to be valid requires that cardiac cells possess the ability to regulate and respond to the active form of vitamin D. The components of the vitamin D system, specifically the VDR, 1 alpha-hydroxylase and 24-hydroxylase, will be examined and the response to hypertrophic stimuli characterized. The importance of vitamin D in cardiovascular function is supported by studies of the vitamin D receptor (VDR) knockout mouse, which develops cardiac hypertrophy. However, the underlying mechanisms involved are difficult to interpret given the pleiotropic effect of vitamin D. To determine the direct effects of endogenous vitamin D on the myocyte will require a tissue specific model, and so a cardiac-selective deletion of the murine VDR gene will be created and the response to a hypertrophic stimulus will be assessed in vivo.